Effects of an inhibitor of poly(ADP-ribose) polymerase, desmethylselegiline, trientine, and lipoic acid in transgenic ALS mice

被引：72

作者：

Andreassen, OA ^{[1
]}

Dedeoglu, A

Friedlich, A

Ferrante, KL

Hughes, D

Szabo, C

Beal, MF

机构：

[1] Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA 02114 USA

[3] Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA

[4] Inotek Corp, Beverly, MA 01915 USA

来源：

EXPERIMENTAL NEUROLOGY | 2001年 / 168卷 / 02期

关键词：

apoptosis; oxidative damage; free radicals; copper; amyotrophic lateral sclerosis; trienterine; lipoic acid; poly(ADP-ribose) polymerase;

D O I：

10.1006/exnr.2001.7633

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The development of transgenic mouse models of amyotrophic lateral sclerosis (ALS) allows the testing of neuroprotective agents. We evaluated the effects of five agents in transgenic mice with the G93A Cu,Zn superoxide dismutase mutation. A novel inhibitor of poly(ADP-ribose) polymerase showed no effects on survival. Desmethylselegiline and CGP3466 are agents that exert antiapoptotic effects in vitro by preventing nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase, They had no significant effects on survival in the G93A mice. Trientine, a copper chelator, produced a modest significant increase in survival, Similarly administration of lipoic acid in the diet produced a significant improvement in survival. These results therefore provide evidence for potential therapeutic effects of copper chelators and lipoic acid in the treatment of ALS. (C) 2001 Academic Press.

引用

页码：419 / 424

页数：6

共 35 条

[1]

Azzouz M, 2000, J NEUROBIOL, V42, P49, DOI 10.1002/(SICI)1097-4695(200001)42:1<49::AID-NEU5>3.0.CO

[2]

2-7

[3] ALS, SOD AND PEROXYNITRITE [J].

BECKMAN, JS ;

CARSON, M ;

SMITH, CD ;

KOPPENOL, WH .

NATURE, 1993, 364 (6438) :584-584

[4] AMYOTROPHIC-LATERAL-SCLEROSIS - RECENT INSIGHTS FROM GENETICS AND TRANSGENIC MICE [J].

BROWN, RH .

CELL, 1995, 80 (05) :687-692

[5] ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions [J].

Bruijn, LI ;

Becher, MW ;

Lee, MK ;

Anderson, KL ;

Jenkins, NA ;

Copeland, NG ;

Sisodia, SS ;

Rothstein, JD ;

Borchelt, DR ;

Price, DL ;

Cleveland, DW .

NEURON, 1997, 18 (02) :327-338

[6] Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1 [J].

Bruijn, LI ;

Houseweart, MK ;

Kato, S ;

Anderson, KL ;

Anderson, SD ;

Ohama, E ;

Reaume, AG ;

Scott, RW ;

Cleveland, DW .

SCIENCE, 1998, 281 (5384) :1851-1854

[7]

Carlile GW, 2000, MOL PHARMACOL, V57, P2

[8]

Chen RW, 1999, J NEUROSCI, V19, P9654

[9] Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia [J].

Eliasson, MJL ;

Sampei, K ;

Mandir, AS ;

Hurn, PD ;

Traystman, RJ ;

Bao, J ;

Pieper, A ;

Wang, ZQ ;

Dawson, TM ;

Snyder, SH ;

Dawson, VL .

NATURE MEDICINE, 1997, 3 (10) :1089-1095

[10] Protective effects of 5-iodo-6-amino-1,2-benzopyrone, an inhibitor of poly(ADP-ribose) synthetase against peroxynitrite-induced glial damage and stroke development [J].

Endres, M ;

Scott, GS ;

Salzman, AL ;

Kun, E ;

Moskowitz, MA ;

Szabó, C .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1998, 351 (03) :377-382

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